Clinical and Radiological Features of Patients with Coronavirus Disease 2019

Background: Conrmed cases of coronavirus disease 2019 (COVID-19) is still increasing, detailed analysis of conrmed cases may be benecial for disease control. Methods: To describe the clinical and radiological ndings of patients conrmed with COVID-19 infection in Haikou, China. Results: A total of 67 patients conrmed with COVID-19 infection were included in this study. 50 were imported cases. Most infected patients presented with fever and cough. The typical CT ndings of lung lesions were bilateral, multifocal lung lesions (52[78%]), with subpleural distribution, and more than two lobes involved (51[78%]). 54 (81%) patients of COVID-19 pneumonia had ground glass opacities. Consolidation was in 30 (45%) patients, crazy paving pattern or interlobular thickening in 17 (25%), adjacent pleura thickening in 23 (34%) patients. Additionally, baseline chest CT did not reveal positive CT ndings in 7 patients (23%), but 3 patients presented unilateral ground glass opacities at follow-up. Importantly, the follow-up CT ndings were tted well with the clinical outcomes. Conclusions: Chest CT could be used as an important tool for early diagnosis of COVID-19, monitoring the disease evolution, judging the treatment effectiveness and predicting the clinical outcomes.


Introduction
In December 2019, a series of pneumonia caused by the Coronavirus disease 2019 (COVID-19) was rst reported in Wuhan, capital of Hubei Province, China. Since then, the COVID-19 spread quickly around the world. By 7 June, 2020, a total of 6,799,713 persons have been con rmed with COVID-19 infection globally. 397,388 people have lost their lives due to the disease. The con rmed cases of COVID-19 are still rising. Since March 4, 2020, WHO have assessed the risk of this event to be very high in both regional and global level, suggesting that the novel coronavirus infections have posed a great threat to global health.
This pneumonia have been con rmed to be caused by a novel enveloped betacoronavirus [1] that has been named as sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 resemble to SARS-CoV [2] and belongs to the family Coronaviridae and the order Nidovirales [3]. Most of the time, the symptoms of human with coronavirus infections are mild, and common cold symptoms are most often seen [4]. However, two betacoronaviruse including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), might result in fatal disaster [5]. Since SARS-CoV-2 is a new member of the coronaviruses, clinical symptoms and CT ndings of patients with SARS-CoV-2 infection may resemble to that of SARS-CoV and MERS-CoV infections, with fever, cough, and radiological ground glass lung opacities [5].
In consideration of the con rmed cases of COVID-19 is still increasing, detailed analysis of con rmed cases may be bene cial for disease control. Plain chest CT is valuable for timely detecting lung lesions, for early treatment. Our purpose is to describe clinical and CT imaging manifestations in 67 con rmed patients with COVID-19 infection in Hainan Island, follow-up CT results and corresponding clinical outcomes.

Patients
The study was approved by the institutional review board of our hospital and written informed consent for was obtained before the retrospective study. All laboratory-con rmed COVID-19 infection patients were enrolled in our study between January 20, 2020, and February 9, 2020 (Fig. 1). The clinical data including age, sex, exposure history, comorbid conditions, symptoms, and laboratory results were collected.

Image acquisition and analysis
All patients underwent plain chest CT in our hospital (Hainan General Hospital). All scans were performed on the NeuViz 128 CT (Neusoft, China) with automatic tube current (300 mA-496 mA). The section thickness was 5 mm; pitch set at 1.5; and breath-hold at full inspiration. Reconstruction was kernel used was lung smooth with a thickness of 1 mm and an interval of 0.8 mm All images were analyzed b two trained radiologists with 14 years, eight years of experience F.C and H.J.C by using the same standard.
Sixty-ve patients underwent follow-up CT scans. The lesions' evolutions of these images were assessed by the same radiologists as described above, using the same standard. According to the CT ndings, the lesions changes were divided into no change, resolution (Figs. 3), rst progression-resolution and progression (Figs. 2). The clinical outcomes were also described.

Results
A total of 67 patients (39 men and 28 women; mean age, 52 years (age range, 28-83 years) were included in this study. Table 1 demonstrates baseline patients' clinical characteristics. Most (91%) were imported cases or have close contact with infected patients; exposure history was unknown in 6 (9%) patients. A majority of patients presented with fever and cough. Seven (10%) patients were asymptomatic at rst. Forty-ve (68%) patients had increased level of C-reactive protein. More than half (52%) patients showed decreased Lymphocyte count.
Chest CT revealed lung lesions in 60 patients at baseline, and 51 (76%) patients had more than two lobes involved. 52(78%) patients had multiple lesions. More than half of the patients had bilateral lung abnormalities, with subpleural distribution. The lesions are mainly distributed in the bilateral lower lobes.

Discussion
We comprehensively analyzed the CT features of 67 patients con rmed with COVID-19 pneumonia in Hainan, an island in the south of China. We detailed described the epidemiologic and clinical features in these patients. Since most of the infected people in our study were imported cases or had close contact with infected patients. Our study provides further evidence of person-to-person transmission in COVID-19 [6,7]. CT manifestation is helpful in early diagnosis of the COVID-19 and valuable for monitoring the disease evolution.
Consistent with recent studies [8,9], our study found that the clinical features of COVID-19 infected patients resemble to that of SARS-CoV, with fever and cough most commonly seen. Gastrointestinal symptoms were uncommon seen, which differed from SARS-CoV, MERS-CoV, and seasonal in uenza [10,11]. We should not neglect the fact that some patients (7%) might be asymptomatic at the early course of the disease. Our ndings provide further supported the notion that the diagnosis of infection could not be ruled out in those patients without clinical symptoms. For the asymptomatic persons with a clear history of exposure to COVID-19, medical observation, home isolation, and further examination should be considered. Besides, we found lymphopenia in 52% of the cases, which was consistent with the results of two recent reports [7,9].
The con rmed cases with COVID-19 is still rapidly increasing across the world. Plain chest CT can discover lung lesions with high sensitivity [12], which is bene cial for early diagnosis and timely treatment. Our ndings revealed some common CT imaging manifestations in patients con rmed with COVID-19 infection: bilateral, multifocal ground glass opacities, with subpleural distribution. Particularly, the lower lobes were the most affected lobes. Pleural effusion, pericardial effusion, cavitation, and lymphadenopathy were uncommon seen in these patients.
The most typical CT ndings of COVID-19 is ground glass opacities. A recent pulmonay pathology study of COVID-19 revealed bilateral diffuse alveolar damage with cellular fbromyxoid exudates in the lung [13]. Therefore, we deduce that the ground glass opacities might be associated with the diffuse alveolar damage including the pulmonary edema, since CT ndings re ect the pathogenesis of viral infection. COVID-19 is a family member of Coronaviridae. Recent studies found that the pathological features of COVID-19 are similar to those seen in SARS and Middle Eastern respiratory syndrome (MERS) coronavirus infection [13]. Thus, it is not surprising that the imaging features of COVID-19 resembles to that of SARS-CoV and MERS-CoV infection. In our study, a majority of patients showed bilateral multifocal involvement, which is tted well with previous studies [14]. SARS and MERS patients are tended to have unilateral involvement [15,16]. More researches should be done to clarify whether this feature is speci c to the COVID-19.
The follow-up CT scan showed that 3 of 7 patients who had negative CT ndings at baseline scan, gradually progressed into unilateral ground glass opacities. Incubation period after infection with the COVID-19 may exist, a patient may be asymptomatic and CT could not detect any abnormalities at this time. At this stage, real-time PCR is crucial for the diagnosis of COVID-19 infection. Similarly, CT could be used to evaluate the disease evolution.
Of note, a few patients in our study had bilateral ground glass opacities in chest CT scans but with negative nucleic acid test for COVID-19. After twice of more times of nucleic acid tests, these patients were nally con rmed with by COVID-19 infection by real-time PCR. When this circumstance occurs, patient's epidemic history, clinical symptoms, imaging features, along with laboratory tests are essential in the diagnosis of the disease. Also, for the patient had negative nucleic acid test but with epidemic history, home isolation is necessary.
CT ndings during follow-up is closely with clinical outcomes. In this study, 65 patients had CT follow-up. Five patients had stable CT ndings during follow-up, 22 patients showed disease resolution and 34 patients showed progression at rst and resolved later all discharged from hospital later. CT scan could be effectively monitoring the disease evolution. Unfortunately, one patient with CT progression died. Two patients did not have CT follow-up because of sever condition and they died about 10 days after admission into the hospital. In conclusion, we found the CT ndings tted well with the clinical outcomes.
Our study had several limitations. Firstly, the sample size is relatively small. Second, most of the patients are imported cases. The difference between imported cases and local cases have not yet been clari ed. Third, most of the patients presented with mild symptoms and they had a favorable outcome nally. Thus, our study could be considered preliminary.

Conclusion
Chest CT could be used as an important tool for early diagnosis of COVID-19, monitoring the disease evolution, judging the treatment effectiveness and predicting the clinical outcomes. The epidemic history of close contact with a COVID-19 infected patient, along with typical CT ndings of bilateral, multifocal, and peripheral ground glass opacities might be an indicator of COVID-19 infection. Therefore, plain chest CT is a useful tool for COVID-19 infection regarding diagnosis and treatment.     Axial CT scans in patients with COVID-19 pneumonia A 55-year-old man of Wuhan local resident travel to Haikou presented with fever and cough for 4 days. a, day 4 after symptom onset: peripheral ground-glass opacity in the bilateral lobes. b, day 6 after symptom onset: Plain chest CT showed ground-glass opacity lesions were partially absorbed. c and d, day 11 and day 26 after symptom onset: CT scan also demonstrated the lesions were gradually resolved. The patient was discharged from hospital on February 6, 11 days after hospitalization.

Figure 4
Axial CT scans in patients with COVID-19 pneumonia A 64-year-old woman of Wuhan local resident travel to Haikou presented with fever for 7 days. a, day 8 after symptom onset: peripheral ground-glass opacity in the bilateral lobes. b, day 10 after symptom onset: Plain chest CT showed multifocal consolidations affecting the bilateral, subpleural lung parenchyma. The patient was admitted into ICU for treatment on this day. c and d, day 28 and day 45 after symptom onset: CT scan also demonstrated the lesions were gradually resolved. The patient was discharged from hospital on February 17, 24 days after hospitalization.